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Expression of SOAT1 in Adrenocortical Carcinoma and Response to Mitotane Monotherapy: An ENSAT Multicenter Study.
- Source :
-
The Journal of clinical endocrinology and metabolism [J Clin Endocrinol Metab] 2020 Aug 01; Vol. 105 (8). - Publication Year :
- 2020
-
Abstract
- Context: Objective response rate to mitotane in advanced adrenocortical carcinoma (ACC) is approximately 20%, and adverse drug effects are frequent. To date, there is no marker established that predicts treatment response. Mitotane has been shown to inhibit sterol-O-acyl transferase 1 (SOAT1), which leads to endoplasmic reticulum stress and cell death in ACC cells.<br />Objective: To investigate SOAT1 protein expression as a marker of treatment response to mitotane.<br />Patients: A total of 231 ACC patients treated with single-agent mitotane as adjuvant (n = 158) or advanced disease therapy (n = 73) from 12 ENSAT centers were included. SOAT1 protein expression was determined by immunohistochemistry on formalin-fixed paraffin-embedded specimens.<br />Setting: Retrospective study at 12 ACC referral centers.<br />Main Outcome Measure: Recurrence-free survival (RFS), progression-free survival (PFS), and disease-specific survival (DSS).<br />Results: Sixty-one of 135 patients (45%) with adjuvant mitotane treatment had recurrences and 45/68 patients (66%) with mitotane treatment for advanced disease had progressive disease. After multivariate adjustment for sex, age, hormone secretion, tumor stage, and Ki67 index, RFS (hazard ratio [HR] = 1.07; 95% confidence interval [CI], 0.61-1.85; P = 0.82), and DSS (HR = 1.30; 95% CI, 0.58-2.93; P = 0.53) in adjuvantly treated ACC patients did not differ significantly between tumors with high and low SOAT1 expression. Similarly, in the advanced stage setting, PFS (HR = 1.34; 95% CI, 0.63-2.84; P = 0.45) and DSS (HR = 0.72; 95% CI, 0.31-1.70; P = 0.45) were comparable and response rates not significantly different.<br />Conclusions: SOAT1 expression was not correlated with clinical endpoints RFS, PFS, and DSS in ACC patients with mitotane monotherapy. Other factors appear to be relevant for mitotane treatment response and ACC patient survival.<br /> (© Endocrine Society 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
- Subjects :
- Adrenal Cortex pathology
Adrenal Cortex surgery
Adrenal Cortex Neoplasms mortality
Adrenal Cortex Neoplasms pathology
Adrenalectomy
Adrenocortical Carcinoma mortality
Adrenocortical Carcinoma pathology
Adult
Antineoplastic Agents, Hormonal therapeutic use
Chemotherapy, Adjuvant methods
Disease-Free Survival
Drug Resistance, Neoplasm
Endoplasmic Reticulum Stress drug effects
Female
Humans
Immunohistochemistry
Male
Middle Aged
Mitotane therapeutic use
Neoplasm Recurrence, Local pathology
Prognosis
Progression-Free Survival
Retrospective Studies
Sterol O-Acyltransferase antagonists & inhibitors
Sterol O-Acyltransferase metabolism
Adrenal Cortex Neoplasms therapy
Adrenocortical Carcinoma therapy
Antineoplastic Agents, Hormonal pharmacology
Mitotane pharmacology
Neoplasm Recurrence, Local epidemiology
Sterol O-Acyltransferase analysis
Subjects
Details
- Language :
- English
- ISSN :
- 1945-7197
- Volume :
- 105
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- The Journal of clinical endocrinology and metabolism
- Publication Type :
- Academic Journal
- Accession number :
- 32449514
- Full Text :
- https://doi.org/10.1210/clinem/dgaa293